The malpighian tubules of Drosophila melanogaster contain the tissue specific enzyme urate oxidase which catalyzes the conversion of uric acid to allantoin. During development this enzyme undergoes marked changes in activity. Urate oxidase is absent in the embryo, first and second instar larvae and pupae while it is present in the third instar larvae and adults. The mechanism regulating the quantity and time of appearance and disappearance of this enzyme are amenable to genetic and biochemical analysis. The experiments proposed herein are designed to test the following hypotheses. First, changes in urate oxidase activity observed during development represent changes in the rate of de novo synthesis of the enzyme. Second, a hemolymph factor (HF) which is probably a purine or pteridine, induces competent third instar larval and adult malpighian tubules to synthesize urate oxidase. The immediate objective of this study is to describe the genetic and molecular mechanisms which regulate the appearance and levels of urate oxidase activity during development of Drosophila. These studies will also lead to a better understanding or uric acid metabolism in humans. One long-term objective of this research program is to determine if HF, once chemically identified, is capable of inducing urate oxidase activity in human liver cells thus providing a means by which pathologies due to excess uric acid may be alleviated.